1. What is Thrombopoietin
Thrombopoietin is also called megakaryocyte growth. The development factor (MGDF) is a protein that is encoded by the Thrombopoietin gene in humans.
The hormone is in most cases written as THPO. Thrombopoietin is a glycoprotein hormone produced by the liver, kidney and bone marrow cells (in small amounts).
It regulates the production of platelets in the human body. The hormone achieves this by activating the differentiation of megakaryocytes, which are the cells in the bone marrow responsible for platelets production.
2. Production of Thrombopoietin
The liver has special cells that handle the production of several hormones such as Thrombopoietin. This organ is the major producer of Thrombopoietin in the human body.
Both the parenchymal cells and sinusoidal cells of the liver play a major role in the production of the hormone. Interleukin augments its production.
Thrombopoietin are also produced but in limited amounts by the kidney. The proximal convoluted tubule cells are the cells responsible for its production in the kidney.
Also, it is produced in limited amounts by the striated muscle and the bone marrow cells. Thus, the primary producers of Thrombopoietin are the liver and the stromal cells in the bone marrow.
3. Functions of Thrombopoietin
Thrombopoietin is mainly responsible for the production of platelets in the human blood. The THPO gene in a human body provides instructions for production of Thrombopoietin, growth, and division of cells, also called the proliferation of cells.
This protein activates the Thrombopoietin receptor, which stimulates several signalling pathways that convey chemical signals to the cell’s nucleus from outside the cell.
The relevance of these pathways is that they control the production of blood cells. Thrombopoietin is mainly useful in the production of a certain type of blood cells called the megakaryocytes; which produce the platelets. The platelets are the component of the blood responsible for blood clotting.
The process can also lead to the renewal of hematopoietic cells that are found in the bone marrow. When renewed, these cells can develop into red blood cells, white blood cells or even more platelets.
The cellular development processes that result in platelets formation is called Megakaryocytopoiesis.
4. Location of the Thrombopoietin gene
The gene that activates the production of Thrombopoietin, which stimulates the production of the blood platelets, is situated on the arm of the chromosome.
In some cases, however, mutations can occur in this chromosome, leading to some hereditary forms of thrombocytosis. This is state whereby the body has a very high platelet count.
In other cases, the platelets and other blood cells may not be completely produced, leading to leukaemia.
5. Thrombopoietin and ITP
ITP (Immune thrombocytopenia) is an autoimmune disorder that affects the platelets. The body produces antibodies that are directed to destroy the produced platelets.
In extreme cases, the body may also produce antibodies to destroy the platelet producing hormones. In this case, the production of platelets will be stopped.
The antibodies are mainly produced in the bone marrow. This will result in excessive bleeding as the body will not be able to prevent excessive bleeding by initiating the clotting process.
The condition is very acute in children and usually resolves spontaneously. It is a chronic condition that requires close monitoring of platelet count in order to avoid blood disorders that can result from excessive bleeding.
6. Thrombopoietin and thrombosis
Thrombosis is a state in which a thrombus also called a blood clot is formed in the blood cells. This usually results from excessive production of platelets among other causes.
Since the number of platelets produced depends on Thrombopoietin, Thrombopoietin has a very important role in the process of thrombosis.
Excessive Thrombopoietin in the body will consequentially result in a higher platelet count. This will increase risks of unusual blood clot or thrombosis development.
If the production of platelets is controlled by regulating the amount of Thrombopoietin in the body, thrombosis can be easily avoided.
- Weber E, Moulis G, Mahévas M, Guy C, Lioger B, Durieu I, Hunault M, Ramanantsoa M, Royer B, Default A, Pérault-Pochat MC, Moachon L, Bernard N, Bardy G, Jonville-Bera AP, Geniaux H, Godeau B, & Cathébras P (2016). Thrombosis during thrombopoietin receptor agonist treatment for immune thrombocytopenia. A French multicentric observational study.
7. Thrombopoietin disorders are hereditary
The Thrombopoietin gene that activates the production of the Thrombopoietin is found on the long arm of the chromosome. It makes thrombopoietin disorders hereditary. This indicates that any disorder in the genes may be passed on from one generation to another.
The disorders may lead to excessive production of platelets that increases the risk of thrombosis that can result in heart attacks or even stroke.
Inversely, the production of platelets may be inhibited by this gene, leading to excessive bleeding cases.
8. Thrombopoietin cannot be used therapeutically
Some patients with very small platelets can undergo a platelet transfusion process. This has proven to be very efficient in most cases.
It is, however, not yet possible to transfer the Thrombopoietin of one person to another to encourage platelet production. Several trials have been made but none of them has been successful.
Some trials have resulted in the volunteers developing autoantibodies to endogenous Thrombopoietin and then develop thrombocytopenia.
The lack of enough Thrombopoietin can only be corrected by a platelet transfusion. Some scientific researchers are currently underway to try and find a way of stimulating platelet formation.
Some peptide analogues are being tested together with other non-peptide ligands that have been seen to act as Thrombopoietin analogues.
9. Gene family of Thrombopoietin gene
Thrombopoietin genes share some traits with other genes in the human body. This makes it fall under a family of genes called endogenous ligands.
A gene family is usually a group of genes that are related and share common characteristics; although, their functions may differ. This helps researchers easily study genes by putting them in a group and studying their relationships.
TPO has, however, proven to be an unusual hematopoietic growth factor as it has some features that cannot be found in the other growth factors. One of the features is that TPO is a very large regulator of blood cells production.
10. Thrombopoietin use in cancer treatment
Though other research works are ongoing, Thrombopoietin has been proven to be a very safe way of treating cancer patients.
Moreover, it has been identified to improve platelet recovery of cancer patients undergoing conventional chemotherapy.
The use of Thrombopoietin in stem cell mobilisation has shown possible reduction in the number of apheresis procedures required.
Its use has also seen a tremendous acceleration in the hematopoietic recovery in recipients with transplanted body organs such as the liver and kidney.
Further scientific trials are being carried out to improve the application of Thrombopoietin as it has proven to be useful in many medical situations. Its approval by FDA as a secondary prophylaxis setting has boosted the interventions in this field.
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